Open lung biopsy in patients on mechanical ventilation
and presenting diffuse pulmonary infiltrate*
ANDREIA SALARINI MONTEIRO**, GABRIELA ADDOR, DAVID HENRIQUE NIGRI, CARLOS ALBERTO DE BARROS FRANCO**
* Study conducted in the Pulmonology Department of the Postgraduate School of Medicine of the Pontificia Universidade Católica in Rio de Janeiro - PUCRJ
**Specialist, as designated by the Sociedade Brasileira de Pneumologia e Tisiologia.
Correspondence to: Andreia Salarini Monteiro. Rua Sorocaba 464 / 402 Botafogo. CEP: 22271-110, Rio de Janeiro, RJ. Phone: 55 21 2266-7392. E-mail: andreiamonteiro@domain.com.br e respirar@pobox.com
Submitted: 30 May 2005. Accepted, after review: 25 February 2005. J Bras Pneumol 2005; 31(3): 212-8.
Key words: Biopsy. Respiratory insufficiency. Respiration artificial.
Background: Open lung biopsy is regarded as the gold standard for the diagnosis of diffuse pulmonary infiltrates. Objective: To determine the diagnostic yield, therapeutic changes, complications and mortality attributed to open lung biopsy in patients with diffuse pulmonary infiltrates and on mechanical ventilation.
Method: We reviewed, retrospectively, the charts of 24 patients, ranging from 26 to 89 years of age, admitted to the intensive care units of two private hospitals and submitted to open lung biopsy.
Results: Diagnostic positivity was found in 100% of patients, resulting in an alteration in the treatment regimen in 75%. Postoperative complications occurred in five patients (20.8%). There were no biopsy-related deaths, although global mortality was 45.8%.
INTRODUCTION
Lung biopsy is an invasive diagnostic procedure and is normally used when other, less-invasive procedures have failed to yield a definitive diagnosis or when a rapid and precise diagnosis is needed(1,2). Lung biopsy through thoracotomy, or open lung biopsy (OLB), allows the surgeon to obtain tissue fragments appropriate for efficient histological, histochemical and even molecular analysis, which is becoming more specialized and allows a more accurate diagnosis. Performed under general anesthesia, OLB requires postoperative pleural drainage for at least 24 hours. A small access incision (minithoracotomy) is used, with no need for resection of the costal arch. The site of choice for conducting the procedure depends on the radiological findings. In cases of diffuse infiltrate, biopsies from one or more sites may be needed(1).
Recommending OLB for critical intensive care unit patients on mechanical ventilation is a difficult decision. The progression of the disease, combined with the need to institute a specific treatment, is an important factor. In such cases, OLB-related morbidity and mortality seem to be minimal(1).
The aim of this study was to evaluate the diagnostic yield, changes in treatment strategy, complications and mortality among patients on mechanical ventilation who presented diffuse pulmonary infiltrate and were submitted to OLB.
METHODS
This was a retrospective study evaluating patients suffering from diffuse pulmonary infiltrate that evolved to acute respiratory insufficiency. These patients were on mechanical ventilation and were submitted to OLB in order to elucidate the diagnosis. The study was conducted from September 1987 to September 2002 and involved patients admitted to the intensive care units of two private hospitals.
A total of 24 patients were included. These patients had previously been submitted to fiberoptic bronchoscopy, which had resulted in no definitive diagnosis and, in some cases, despite the treatment instituted (antibiotic therapy based on culture results), was followed by progressive worsening.
In 13 patients (54.2%), the OLB was conducted in an operating room. In the remaining 11 patients (45.8%), the procedure was carried out in the intensive care unit itself due to the high risk involved in transporting those patients.
The biopsies were conducted by different chest surgeons, under general anesthesia and using minithoracotomy. In all cases, suture of the lung was performed with surgical staples.
A fragment of lung tissue was obtained from the site presenting the greatest degree of involvement in the computed tomography scan of the chest. In all cases, a pathologist was present at the time of the procedure in order to evaluate the quality of the material obtained. The material was then sent for histopathological study, direct exam and culture (for pyogenic germs, mycobacteria and fungi), immunofluorescence for atypical germs (Legionella sp., Mycoplasma sp. and Chlamydia sp.) and, in suspect cases, for virus culture (using HEp2 cells in Eagle Hanks medium supplemented with bovine fetal serum).
RESULTS
A total of 24 patients (12 men and 12 women) were included in the study (Table 1). The mean age was 65.9 years (range, 26 to 89).
A total of 11 patients (45.8%) were considered immunocompromised (7 suffered from malignant neoplasia, 3 made chronic use of corticosteroids, and 1 presented both characteristics).
The conduction of OLB In this group of patients, OLB resulted in diagnosis in 100% of the cases (Table 2).
Two patients presented more than one diagnosis: one presented acute respiratory distress syndrome (ARDS) accompanied by pneumococcal pneumonia, whereas the other presented ARDS accompanied by pneumonia caused by Pneumocystis carinii.
Five patients (20.8%) presented complications related to the procedure: 1 with pleural empyema due to Staphylococcus aureus and 4 with bronchopleural fistula. Of the 4 patients who developed bronchopleural fistula, 3 were diagnosed with ARDS.
There were no deaths directly related to the diagnostic procedure.
After the results of the OLB were known, there was a treatment strategy change, defined as the introduction or withdrawal of a particular drug, in 18 cases (75%). Global mortality, during the hospitalization period in the intensive care unit was 45.8% (11 patients) (Figure 2). One of the deaths occurred due to the progression of the underlying disease (multiform glioblastoma) after reduction of the pulmonary infiltrate. A total of 13 patients were discharged from the intensive care unit and were later discharged from the hospital (54.2%).
Among the 11 patients who died, the treatment regimen was not changed after the OLB in 5 (45.4%).
In contrast, among the 13 (54.2%) who survived, the treatment remained unchanged in only 1 (7.7%). Eleven patients (45.8%) were considered immunocompromised, of which 7 (63.6%) underwent a change in treatment and 3 (27.2%) presented complications. Of those 11, 8 (72.7%) died.
Of the 13 immunocompetent patients (54.2% of the cases), 11 (84.6%) underwent a change in treatment, 2 (15.3%) presented complications and 3 (23%) died.
DISCUSSION
It is rare for OLB to be performed in an intensive care unit, the annual incidence in the USA ranging from 0% to 0.9%(4). Despite the fact that these patients were all in critical condition, the procedure proved safe and provided high positivity for the diagnosis of diffuse pulmonary infiltrate(4,5). The decision to perform OLB in patients on mechanical ventilation is made based on the need to obtain a precise diagnosis and TABLE 1
Patients included in the evaluation
Patient Gender Age Diagnosis at ICU Admission
1 Male 87 Adenovirus Pneumonia
2 Female 75 Lung squamous cell carcinoma + diffuse interstitial infiltrate 3 Female 80 Pneumonia caused by Chlamydia sp.
4 Female 44 Community-acquired pneumonia caused by Mycoplasma sp.
+ corticosteroid use
5 Male 84 Bronchial aspiration in abdominal surgery postoperative period 6 Male 70 Severe community-acquired pneumonia
7 Male 86 Severe community-acquired pneumonia 8 Female 77 Diffuse interstitial infiltrate
9 Male 29 Severe community-acquired pneumonia 10 Female 66 Diffuse interstitial infiltrate
11 Male 69 Non-Hodgkin’s lymphoma
12 Male 58 Idiopathic pulmonary fibrosis + corticosteroid use 13 Male 59 Bladder Carcinoma and Taxol use + pneumonia 14 Male 83 Rheumatoid arthritis + pulmonary fibrosis 15 Female 49 Severe community-acquired pneumonia
16 Female 82 Idiopathic pulmonary fibrosis + corticosteroid use 17 Female 75 COPD + multiple myeloma + Diffuse pulmonary infiltrate 18 Female 60 Non-Hodgkin’s lymphoma
19 Female 26 Severe community-acquired pneumonia 20 Female 59 Diffuse interstitial infiltrate
21 Male 89 Severe community-acquired pneumonia
22 Male 72 Fungal infection
23 Male 47 Multiform glioblastoma + use of corticosteroid
+ pneumonia caused by P. carinii + diffuse interstitial infiltrate 24 Female 56 Lung adenocarcinoma + chemotherapy
therefore offer specific treatment (avoiding the harmful effects or inefficiency of empirical treatment) or even on the desire to obtain prognostic information(4,6).
There is no consensus regarding the timing of the OLB(4,7,8). The biopsy site should be determined based on the radiological findings so that only a small fragment need be collected(9,10). Biopsy samples taken from the lingula or medial lobe yield results equivalent to those taken from other sites(9,11,12). To be adequate for histological and bacteriological analysis, the tissue sample should measure at least 3 x 2 x 1 cm(3,13).
Despite their similar efficiency, OLB was chosen over video-assisted thoracoscopy in these patients due to the shorter time needed for conducting the procedure, together with the fact that there was neither the need to change the orotracheal tube to one with a double lumen nor the need to selectively ventilate one lung(7,14-16).
For the diagnosis of diffuse pulmonary infiltrate, OLB is regarded as the gold standard (1,4,7-9,17). In the literature, its positivity varies from 80%
to 94%, whereas that of procedures using fiberoptic bronchoscopy (bronchoalveolar lavage, bronchial brush and transbronchial biopsy) ranges from 38% to 85%(4). Transbronchial biopsy in patients on mechanical ventilation may be safely conducted, although its diagnostic efficiency is only 48%, with no significant improvement even when the number of collected tissue samples is doubled(18-20).
Diagnostic positivity in our study was 100%, and only two patients presented more than one concomitant diagnosis (8.3% of the cases). Flabouris et al.(4) also studied 24 patients with re s p i ra t o r y i ns u f f i c i e n c y, o n m e c h a n i c a l ventilation and submitted to OLB and found 92% diagnostic positivity (the histopathology was normal in 8% of the cases). Canver et al.(21) TABLE 2
Diagnosis and evolution after OLB
Patient Diagnosis after OLB Change in treatment Outcome
1 Idiopathic pulmonary fibrosis No Death
2 Pneumonitis caused by drug use No Death
3 Desquamative interstitial pneumonia Yes Discharge
4 ARDS Yes Discharge
5 ARDS Yes Discharge
6 ARDS + pneumonia caused by pneumococci Yes Discharge
7 Infectious pneumonia No Discharge
8 Churg-Strauss syndrome Yes Discharge
9 Pneumonia caused by Mycoplasma sp. Yes Discharge
10 Desquamative interstitial pneumonia Yes Discharge
11 Small cell carcinoma No Death
12 Idiopathic pulmonary fibrosis No Death
13 Pneumonitis caused by drug use Yes Death
14 ARDS Yes Death
15 Pneumonia caused by Legionella sp. Yes Discharge
16 Idiopathic pulmonary fibrosis Yes Discharge
17 ARDS + pneumonia caused by P. carinii Yes Death
18 Pneumonitis caused by drug use Yes Death
19 Pneumonia caused by P. carinii Yes Discharge
20 Poorly differentiated carcinoma metastasis No Death
21 Acute interstitial pneumonia (Hamman-Rich) Yes Death
22 Churg-Strauss syndrome Yes Discharge
23 ARDS Yes Death
24 Pneumonitis caused by drug use Yes Discharge
evaluated 27 respiratory insufficiency patients on mechanical ventilation and found OLB to present 100% positivity. Diagnostic positivity of OLB in patients on mechanical ventilation is comparable to that found in patients with diffuse pulmonary infiltrate and not on ventilatory support(9,10,22).
Based on the OLB results, treatment regimens w e r e a d j u s t e d i n 1 8 c a s e s ( 7 5 % ) , i n f u l l concordance with the results obtained by Flabouris et al.(4) and comparable to the 67% found by Canver et al.(21) (67%).
Atelectasis, bronchopleural fistula, empyema and hemothorax have all been associated with OLB(1,4,7-9). Five of our patients (20.8%) presented such complications, bronchopleural fistula being the most common (4 cases). Flabouris et al.(4) reported complications in 17% of patients and prolonged air leakage in all patients. One of the
patients presented excessive bleeding in the immediate postoperative period, requiring surgical reintervention and dying some hours later. Canver et al.(21) observed complications in 40% of patients, prolonged air leakage being the most frequent. Being on mechanical ventilation does n o t s e e m t o i n c r e a s e t h e f r e q u e n c y o f complications. In the studies reviewed, in which patients with diffuse pulmonary infiltrate and not on mechanical ventilation were submitted to OLB and subsequently evaluated, complications were observed in less than 18%(8,23-26). Most patients who presented complications were diagnosed with ARDS. Chuang et al.(27) observed a higher frequency of complications in patients with ARDS. Patel et al.(28) recently published a study involving 57 patients with ARDS who underwent OLB and showed the frequency of complications to be 39%, Figure 1. Diagnoses after open lung biopsy
Figure 2. Clinical evolution of patients submitted to open lung biopsy
0% 10% 20% 30% 40% 50% 60% 70% 80% 90%
m 0%
10% 20% 30% 40% 50% 60% 70% 80% 90%
m udanç tratam e 16,60%
8,30%
16,60% 12,50%
29,10%
16,60%
ARDS
ARDS + Pneumonia
Pneumonia
Pneumonitis from drug use
Idiophatic pulmonary fibrosis
Other
0% 10% 20% 30% 40% 50% 60% 70% 80% 90%
overall
immunocropromised
imunocompetent
a result similar to those published by other authors(21,28).
Intraoperative mortality in the present study was 0%. This is in agreement with reports from other authors, including those who evaluated patients with diffuse pulmonary infiltrate and not on mechanical ventilation(4,7-9,22).
Global mortality in the present study was 45.8%, lower than the 67% and 52% found by other authors(4,21). Of the patients who survived, post-OLB changes in treatment were made in 92.3% of cases (Table 3). Flabouris et al.(4) observed that treatment regimens had been changed for 88% of the survivors, and the chi-square test showed a strong, albeit less than significant, tendency toward lower mortality when treatment regimens were changed based on OLB findings.
In the present study, the mortality rate among patients considered immunocompromised was higher than that observed in immunocompetent patients (72.7% and 27.2%, respectively), in contrast to the findings of Walker et al.(8) and Wagner et al.(22), who found no such difference. This difference in mortality may be explained by of the fact that the patients in the present study were in more critical condition since the authors cited above evaluated immunocompromised patients with diffuse pulmonary infiltrate that were not on mechanical ventilation.
The most common diagnoses among our patients were ARDS (6 cases; 25%) and pneumonia (6 cases; 25%). Corticosteroid therapy was initiated in four patients who presented ARDS phases 2 and 3 and after associated infection had been disregarded. In the other two patients diagnosed with ARDS, corticosteroid therapy was initiated in association with the treatment for pneumonia due to P. carinii, defined as PaO2 < 70 mmHg. The diagnosis of bacterial pneumonia was made through tissue culture in only one case (4.1%). The positivity of lung tissue culture is normally low, varying from 0% to 4% in the literature(9).
We can conclude that OLB is a procedure presenting low mortality and morbidity and may be safely conducted in patients on mechanical ventilation. The impact of OLB on the mortality of these patients has not yet been established in the literature. However, of the methods available for evaluating such patients, OLB presents the highest diagnostic positivity.
The benefit of OLB should be evaluated not only in terms of improving median survival but a l s o i n v i e w o f t h e v a l u a b l e p r o g n o s t i c information obtained.
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